NM_014225.6:c.79-5757T>C

Variant names:

• chr19-52196187-T-C
• rs6509626
• NM_014225.6:c.79-5757T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014225.6(PPP2R1A):​c.79-5757T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 149,278 control chromosomes in the GnomAD database, including 51,784 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.84 (51784 hom., cov: 32)
• Consequence: PPP2R1A NM_014225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 7 publications found

Genes affected

PPP2R1A (HGNC:9302): (protein phosphatase 2 scaffold subunit Aalpha) This gene encodes a constant regulatory subunit of protein phosphatase 2. Protein phosphatase 2 is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The constant regulatory subunit A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. This gene encodes an alpha isoform of the constant regulatory subunit A. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2010]

PPP2R1A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Houge-Janssens syndrome 2

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Illumina, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R1A	NM_014225.6	c.79-5757T>C		intron_variant	Intron 1 of 14	ENST00000322088.11	NP_055040.2
PPP2R1A	NR_033500.2	n.124-5757T>C		intron_variant	Intron 1 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R1A	ENST00000322088.11	c.79-5757T>C		intron_variant	Intron 1 of 14	1	NM_014225.6	ENSP00000324804.6

Frequencies

GnomAD3 genomes AF: 0.838 AC: 124951 AN: 149164 Hom.: 51735 Cov.: 32

Gnomad AFR AF: 0.918

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.821

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.838 AC: 125053 AN: 149278 Hom.: 51784 Cov.: 32 AF XY: 0.835 AC XY: 60902 AN XY: 72958

African (AFR) AF: 0.918 AC: 37867 AN: 41260

American (AMR) AF: 0.705 AC: 10437 AN: 14814

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 2727 AN: 3376

East Asian (EAS) AF: 0.758 AC: 3909 AN: 5156

South Asian (SAS) AF: 0.836 AC: 3958 AN: 4736

European-Finnish (FIN) AF: 0.818 AC: 8495 AN: 10390

Middle Eastern (MID) AF: 0.782 AC: 222 AN: 284

European-Non Finnish (NFE) AF: 0.829 AC: 55000 AN: 66324

Other (OTH) AF: 0.821 AC: 1688 AN: 2056

Alfa AF: 0.879 Hom.: 106048

Bravo AF: 0.880

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.58
DANN	Benign	0.59
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6509626; hg19: chr19-52699440;